Dr. Randis is a Neonatologist and Assistant Professor of Pediatrics at Columbia University whose current investigative efforts are directed towards elucidating the pathogenic mechanisms underlying the development of bacterial vaginosis (BV). BV, the most common vaginal infection worldwide, is associated significant adverse sequelae including preterm birth. The association of BV with the onset of preterm labor is of major public health importance as BV has been estimated to cause 90,000 excess preterm births per year. Recently, maternal vitamin D deficiency has been linked to the development of BV during the first trimester of pregnancy. Vitamin D is an important regulator of innate immune response and deficiencies of this critical vitamin have been associated with an increased susceptibility to other infectious diseases. The role of vitamin D in the pathogenesis of BV may be of particular relevance in explaining the striking racial disparities in the prevalence of BV. African-American populations, which are at highest risk for vitamin D-deficiency, also have the highest prevalence of BV and BV-associated preterm birth. Identification of potentially modifiable risk factors for BV represents a unique opportunity to reduce the burden of this exceedingly prevalent disease and its associated morbidities. These observations have led the candidate to formulate the primary hypothesis of this research proposal: that vitamin D deficiency is a significant risk factor for the development of BV in healthy adult women and that this effect is mediated by a deficiency of vitamin D-responsive immune mediators. The primary aims of this proposal are 1) to investigate the role of vitamin D status in the development of BV in a cohort of non-pregnant, healthy adult women, 2) to explore specific molecular mechanisms by which vitamin D signaling controls vaginal innate immune responses relevant to BV, and 3) to determine whether vitamin D-responsive antimicrobial peptides mediate the observed association between vitamin D deficiency and bacterial vaginosis in pregnant women. This research proposal represents a critical step in attaining the candidate's long-term goal: to transition to an independent research career focused on mechanistic and translational studies of preterm birth. Superb mentorship, participation in the Master's program in Patient Oriented Research, and continued access to the abundant resources and rich intellectual environment across departments and schools at Columbia University leave this candidate well-positioned to achieve this goal. This Career Development Award will serve as a driving force in Dr. Randis'success, providing the protected time and additional training required for this candidate to become an independent investigator. PUBLIC HEALTH RELEVANCE: Project Narrative Bacterial vaginosis is the most common vaginal infection worldwide, and is associated with significant adverse sequelae, including preterm birth and acquisition of sexually transmitted diseases. This proposal is designed to explore the hypothesis that vitamin D deficiency is a significant risk factor for the development of bacterial vaginosis in healthy adult women. Identification of potentially modifiable risk factors for bacterial vaginosis represents a unique opportunity to reduce the burden of this exceedingly prevalent disease and its associated morbidities.